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bioRxiv · 10.1101/2025.08.01.667938

The effects of chronic social stress on cognitive flexibility in adult female macaques

Alvarado, M. C.·Jonesteller, T.·Bailey, K.·Gray, A. C.·Sanchez, M. M.·Bachevalier, J.
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Abstract

Chronic social subordination stress in macaques, particularly beginning early in life, is associated with negative health and cognitive aging outcomes. Utilizing a longitudinal, translational monkey model of early life stress in Rhesus macaques (Macaca mulatta), we assessed adult female cognitive performance that had received social subordination stress associated with Low Social Status (LSS) since birth. This chronic social stress in lower ranked monkeys produces physiological stress responses that over time can accelerate biological and cognitive aging. We compared 14 adult females of Low Birth Rank that had received higher levels of social subordination stress since infancy with 11 adult females of High Birth Rank that had received lower levels of chronic social stress. We followed these two groups longitudinally from birth to adolescence to assess long-term behavioral, physiological, and neural consequences of social stress. As they reached adulthood (ages 7-8 years), we measured executive function/cognitive flexibility using the Intra-/Extra-dimensional shift task (ID/ED), relevant for age-related cognitive decline. Only mild differences between High and Low ranking subjects were observed on the simple discrimination, and the reversal learning stages of the task. We did find an interaction between High Birth Rank and performance across the three dimensional-shift stages that was not present in the low-ranking subjects. Thus, although at this first age, we did not yet detect the presence of accelerated cognitive decline following chronic social stress, the low-ranking females showed mild deficits in cognitive flexibility compared to high-ranking subjects. We discuss additional factors impacting performance, and comparisons with neuroimaging data.

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Alvarado, M. C., Jonesteller, T., Bailey, K., Gray, A. C., Sanchez, M. M., Bachevalier, J.. 2025-08-01. The effects of chronic social stress on cognitive flexibility in adult female macaques. https://doi.org/10.1101/2025.08.01.667938

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